Although targeted therapies have been tested, to date, there is no effective therapy to stop therapy-resistant tumor recurrence or reseeding. Single targeted therapy that can stop tumor “reseeding” of therapy-resistant tumors as seen in recurrent glioblastoma and in peritoneal carcinomatosis, such as occurs in pancreatic cancer, ovarian and gastric cancers provide a novel approach. Even if the primary tumors responded to current therapies, tumor recurrence usually results in therapy-resistant tumors—as seen in, for example, recurrent glioblastoma, pancreatic cancer, triple negative breast cancer (TNBC), and peritoneal carcinomatosis. Similarly, circulating tumor cells have been increasingly described, and serve as prognostic markers, but no therapy exists to inhibit them and prevent metastatic tumor initiation. Likewise, microvascular leakiness in tumors contributes to poor therapy delivery while facilitating egress of circulating tumor cells, but no significant therapy exists to address this. The basic rationale is that these cancer trends for recurrence can best be inhibited by a single-agent that can simultaneously inhibit tumor initiation, therapy resistance, and microvessel leakiness.
In parallel, there is no therapy for patients with microvessel leakiness, disruption, and/or microbleeds in the brain that progress to major bleeds as seen in ischemic stroke patients (post-ischemic hemorrhagic transformation or hemorrhagic conversion). In fact, a known complication of the FDA-approved thrombolytic tissue-plasminogen activator (TPA)-therapy for ischemic stroke when given late is hemorrhagic transformation. Once initiated, micro-to-macrobleed initiation-progression, or hemorrhagic transformation, leads to death even if the initiating ischemic insult is resolved by current stroke thrombolytic therapy. There too is no therapy for patients with brain microvessel leakiness, disruption, and/or microbleeds (detected on MRI) which are associated with subsequent pathologies, such as, but not limited to stroke. The basic rationale is that microvessel leakiness, microbleeds and progression to hemorrhagic transformation or other microbleed-associated pathologies can best be stopped or prevented by preventing development of microbleeds and their progression to macrobleeds—collectively represented by microvacular leakiness, loss of integrity, and neutrophil-mediated injury.